Ehtesham, E.

Medicine

May 2017

Introduction: Polyphenols have been suggested as being able to modulate the risk of cardiovascular disease. However, the molecular mechanisms underlying these effects are unclear and the literature lacks consistency and reproducibility, with in vitro studies being unable to account for factors such as bioavailability and metabolism seen in vivo.

Methods: This doctoral thesis was a clinic-laboratory body of work investigating the effects of polyphenols (Oligopin®) on endothelial function using a dose of Oligopin® in the physiological range. Human umbilical vein endothelial cells (HUVEC) were used for the in vitro work. To examine the possible translation of the in vitro work, endothelial function assessed by flow mediated dilatation (FMD) and reactive hyperaemia peripheral arterial tonometry (RH-PAT) was compared in individuals with and without polycystic ovary syndrome. A double blind placebo controlled phase 1 clinical trial (ClinicalTrails.gov Identifier: NCT02116816) was undertaken in healthy volunteers to investigate the effects of the Oligopin® in vivo. Endothelial function was determined by the reactive hyperaemic index (RHI) and augmentation index (AI).

Results: Oligopin® improved endothelial function in vitro by increasing endothelial nitric oxide synthase activity (p-value=0.0066) and decreasing superoxide production (p-value=0.0361) resulting in increased nitric oxide concentration (p-value = 0.0286). There were no differences in endothelial function measurements between PCOS and controls for either FMD (6.9±3.1 vs 5.7±3.1% (p-value=0.14) and RHI (2.0±0.7 vs 2.2±0.7 (p-value=0.51) respectively. There were no differences observed after Oligopin® treatment in the clinical trial in healthy volunteers for either marker of endothelial function.

Conclusions: Treatment of HUVEC in an in vitro model showed that Oligopin® may have a beneficial effect on endothelial function by increasing endothelial nitric oxide production. Both FMD and RH-PAT were shown to be equivalent in measuring in vivo endothelial function. However, in a phase 1 clinical trial, Oligopin® appeared not to have any in vivo biological activity on the cardiovascular risk factors measured.

Publisher

Hull York Medical School, The University of Hull and University of York